Galectin-14 promotes hepatocellular carcinoma tumor growth via enhancing heparan sulfate proteoglycan modification  

作　　者：Liming Gou Gang Yang Sujuan Ma Tong Ding Luan Sun Fang Liu Jin Huang Wei Gao 

机构地区：[1]Jiangsu Key Lab of Cancer Biomarkers,Prevention and Treatment,Collaborative Innovation Center for Personalized Cancer Medicine,Key Laboratory of Human Functional Genomics of Jiangsu Province,National Health Commission Key Laboratory of Antibody Techniques,School of Basic Medical Sciences,Nanjing Medical University,Nanjing,Jiangsu 211166,China [2]Core Laboratory,the Affiliated Sir Run Run Hospital of Nanjing Medical University,Nanjing,Jiangsu 211166,China [3]Department of Gastroenterology,the Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University,Changzhou Medical Center of Nanjing Medical University,Changzhou,Jiangsu 213000,China

出　　处：《The Journal of Biomedical Research》2023年第6期418-430,共13页生物医学研究杂志（英文版）

基　　金：The current study was supported by the National Natural Science Foundation of China(Grant Nos 81972284 and 82273239);the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(Grant No.22KJB310001);Nanjing Medical University Science and Technology Development Foundation(Grant Nos.NMUB-20220050 and NMUB20210006).

摘　　要：Hepatocellular carcinoma(HCC)is a highly heterogeneous malignancy and lacks effective treatment.Bulk-sequencing of different gene transcripts by comparing HCC tissues and adjacent normal tissues provides some clues for investigating the mechanisms or identifying potential targets for tumor progression.However,genes that are exclusively expressed in a subpopulation of HCC may not be enriched or detected through such a screening.In the current study,we performed a single cell-clone-based screening and identified galectin-14 as an essential molecule in the regulation of tumor growth.The aberrant expression of galectin-14 was significantly associated with a poor overall survival of liver cancer patients with database analysis.Knocking down galectin-14 inhibited the proliferation of tumor growth,whereas overexpressing galectin-14 promoted tumor growth in vivo.Non-targeted metabolomics analysis indicated that knocking down galectin-14 decreased glycometabolism;specifically that glycoside synthesis was significantly changed.Further study found that galectin-14 promoted the expression of cell surface heparan sulfate proteoglycans(HSPGs)that functioned as co-receptors,thereby increasing the responsiveness of HCC cells to growth factors,such as epidermal growth factor and transforming growth factor-alpha.In conclusion,the current study identifies a novel HCC-specific molecule galectin-14,which increases the expression of cell surface HSPGs and the uptake of growth factors to promote HCC cell proliferation.

关 键 词：hepatocellular carcinoma galectin-14 heparan sulfate proteoglycans CO-RECEPTOR 

分 类 号：R735.7[医药卫生—肿瘤]